Computational model combined with in vitro experiments to analyse mechanotransduction during mesenchymal stem cell adhesion

TL;DR

This study combines computational modeling and in vitro experiments to analyze how mechanical signals during mesenchymal stem cell adhesion influence cell shape, cytoskeleton reorganization, and mechanotransduction pathways, aiding biomaterial design.

Contribution

It introduces the Cytoskeleton Divided Medium (CDM) model to quantitatively simulate cell adhesion mechanics and cytoskeleton dynamics during spreading.

Findings

Intracellular tension and focal adhesion forces increase with cell spreading.

The model predicts cytoskeleton reorganization during cell spreading.

Mechanical signals correlate with cell shape and differentiation potential.

Abstract

The shape that stem cells reach at the end of adhesion process influences their differentiation. Rearrangement of cytoskeleton and modification of intracellular tension may activate mechanotransduction pathways controlling cell commitment. In the present study, the mechanical signals involved in cell adhesion were computed in in vitro stem cells of different shapes using a single cell model, the so-called Cytoskeleton Divided Medium (CDM) model. In the CDM model, the filamentous cytoskeleton and nucleoskeleton networks were represented as a mechanical system of multiple tensile and compressive interactions between the nodes of a divided medium. The results showed that intracellular tonus, focal adhesion forces as well as nuclear deformation increased with cell spreading. The cell model was also implemented to simulate the adhesion process of a cell that spreads on protein-coated substrate by emitting filopodia and creating new distant focal adhesion points. As a result, the cell model predicted cytoskeleton reorganisation and reinforcement during cell spreading. The present model quantitatively computed the evolution of certain elements of mechanotransduction and may be a powerful tool for understanding cell mechanobiology and designing biomaterials with specific surface properties to control cell adhesion and differentiation.